Mechanism of Action: The antiemetic properties of metoclopramide appear to be a result of its antagonism of central and peripheral dopamine receptors.

Dopamine produces nausea and vomiting by stimulation of the medullary chemoreceptor trigger zone (CTZ), and metoclopramide blocks stimulation of the CTZ by agents like l-dopa or apomorphine which are known to increase dopamine levels or to possess dopamine-like effects. Metoclopramide also abolishes the slowing of gastric emptying caused by apomorphine. Like the phenothiazines and related drugs, which are also dopamine antagonists, metoclopramide produces sedation and may produce extrapyramidal reactions, although these are comparatively rare. Metoclopramide inhibits the central and peripheral effects of apomorphine, induces release of prolactin and causes a transient increase in circulating aldosterone levels, which may be associated with transient fluid retention. The onset of pharmacological action of metoclopramide is 1 to 3 minutes following an intravenous dose, 10 to 15 minutes following intramuscular administration, and 30 to 60 minutes following an oral dose; pharmacological effects persist for 1 to 2 hours. Dosage - Children: Gastroesophageal reflux: Oral: 0.1-0.2 mg/kg/dose up to 4 times/day; efficacy of continuing metoclopramide beyond 12 weeks in reflux has not been determined; total daily dose should not exceed 0.5 mg/kg/day Gastrointestinal hypomotility (gastroparesis): Oral, I.M., I.V.: 0.1 mg/kg/dose up to 4 times/day, not to exceed 0.5 mg/kg/day Antiemetic (chemotherapy-induced emesis) (unlabeled): I.V.: 1-2 mg/kg 30 minutes before chemotherapy and every 2-4 hours, for a total of 5 doses (5-10 mg/kg) daily Post-pyloric feeding tube placement (unlabeled) : I.V.: <6 years: 0.1 mg/kg. 6-14 years: 2.5-5 mg. Dosage - Adults: Gastroesophageal reflux: Oral: 10-15 mg/dose up to 4 times/day 30 minutes before meals or food and at bedtime; single doses of 20 mg are occasionally needed for provoking situations Gastrointestinal hypomotility (gastroparesis): Oral: 10 mg 30 minutes before each meal and at bedtime for 2-8 weeks. I.V. (for severe symptoms): 10 mg over 1-2 minutes; 10 days of I.V. therapy may

be necessary for best response Antiemetic (chemotherapy-induced emesis) (unlabeled) : I.V.: 1-2 mg/kg 30 minutes before chemotherapy and every 2-4 hours, for a total of 5 doses (5-10 mg/kg) daily Postoperative nausea and vomiting (unlabeled) : I.M., I.V.: 10 mg near end of surgery; 20 mg doses may be used Post-pyloric feeding tube placement (unlabeled): I.M., I.V.: 10 mg Elderly: Gastroesophageal reflux: Oral: 5 mg 4 times/day (30 minutes before meals and at bedtime); increase dose to 10 mg 4 times/day if no response at lower dose Gastrointestinal hypomotility: Oral: Initial: 5 mg 30 minutes before meals and at bedtime for 2-8 weeks; increase if necessary to 10 mg doses. I.V.: Initiate at 5 mg over 1-2 minutes; increase to 10 mg if necessary Postoperative nausea and vomiting (unlabeled): I.M.: 5 mg near end of surgery; may repeat dose if necessary Dosing adjustment in renal impairment: Clcr 10-40 mL/minute: Administer at 50% of normal dose Clcr<10 mL/minute: Administer at 25% of normal dose Hemodialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary Supplied Injection, solution, as hydrochloride (Reglan): 5 mg/mL (2 mL, 10 mL, 30 mL). Syrup, as hydrochloride: 5 mg/5 mL (10 mL, 480 mL) [some products contain sodium benzoate; sugar free] Tablet, as hydrochloride (Reglan): 5 mg, 10 mg